ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Obsessive-compulsive disorder (OCD) is a brain disorder with recognizable periods of onset, course, familial occurrence, epidemiology, phenomenology, and treatment response. Several manifestations of pathophysiology are beginning to be defined, although they may represent intermediate pathophysiology rather than primary etiology. Positron emission tomography studies have consistently identified hypermetabolism in the orbitofrontal cortex, caudate nucleus, and, sometimes, anterior cingulate cortex. Neuropsychologic testing frequently identifies abnormalities in visuospatial function. Abnormal levels of cerebrospinal fluid neurotransmitters and neuromodulators are identifiable in untreated patients with OCD and return toward normal levels after effective treatment. The most consistent pathophysiologic finding in OCD points toward an abnormality in serotonin neurotransmission. Therapeutic response to selective serotonin reuptake inhibitors and the absence of improvement with norepinephrine reuptake inhibitors and dopamine antagonists argue strongly for a role of serotonin in the pathophysiology and treatment of OCD. Despite this clear indication from treatment trials, probes and manipulations of the serotonin system and its specific receptors have not provided a useful understanding of specific abnormalities. Clomipramine or potent selective serotonin reuptake inhibitors are the pharmacotherapy of choice for OCD, with a more limited role reserved for monoamine oxidase inhibitors. If one selective serotonin reuptake inhibitor is ineffective, others may be beneficial, in addition to the different proserotonergic and nonserotonergic augmentation strategies that could be useful in treatment of resistant OCD patients. Nondrug therapies are also important in OCD: behavioral therapy is frequently helpful and neurosurgery is sometimes helpful when other treatments fail.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We determined whether methylphenidate, a dopamine transporter blocker, modifies motor, cognitive, or affective responses to L-Dopa in Parkinson's disease (PD). Five patients who reported benefit from L-Dopa/carbidopa and motor fluctuations were admitted and withdrawn from their usual antiparkinsonian medications. On 3 consecutive days in a randomized double-blinded fashion, they took 0.2 mg/kg oral methylphenidate or placebo followed 30 minutes later by a 1-hour intravenous L-Dopa (2 mg/kg per h) or placebo infusion. Vital signs, tapping, walking, dyskinesias, mood, anxiety, concentration, and arousal were monitored every 30 minutes. Cognitive testing was performed before and following the infusion. Methylphenidate combined with L-Dopa led to greater peak right-hand tapping speed than either alone. Dyskinesia severity increased most when methylphenidate and L-Dopa were co-administered. There were no differences between conditions on the Stroop test, digit ordering, simple reaction time, or covert orienting of attention validity effect. Methylphenidate alone led to improvement in choice reaction time. Change in self-assessed analogue ratings of mood, anxiety, arousal, or concentration did not differ between conditions. Methylphenidate increased the motor effects of L-Dopa with minimal effects on cognitive or affective functions, suggesting a physiologic role for the dopamine transporter in patients with PD with motor fluctuations.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The efficacy and safety of two dosages of tolcapone were compared in a 12-week crossover trial involving 118 nonfluctuating patients with PD on a stable dose of levodopa (L-Dopa). At trial onset, all patients received open-label tolcapone 100 mg three times daily for 4 weeks. At week 4, 116 eligible patients entered an 8-week double-blind treatment period and were randomized to receive tolcapone three times daily at either 100 mg (group 1;n= 58) or 200 mg (group 2;n= 58) until week 8, followed by the alternative tolcapone dosage until week 12. Ratings included Unified Parkinson's Disease Rating Scale (UPDRS), Schwab & England, and patient diaries, assessed at baseline and at 4, 8, and 12 weeks. At week 4, the investigator's global assessment (IGA) of efficacy showed improvement in 76% of patients. The mean total daily L-Dopa dose and mean UPDRS scores for subscales II and III decreased significantly (p< 0.001). During the double-blind treatment period, IGA showed improvements at either or both dosages in 61% of patients; further changes in other efficacy variables were minimal and were similar with both tolcapone dosages. The most frequent adverse events were dopaminergic (nausea and dyskinesia); the most frequent nondopaminergic adverse event was diarrhea. The incidence of adverse events during double-blind treatment was slightly higher with tolcapone 200 mg three times daily (33%) than with tolcapone 100 mg three times daily (24%). The authors conclude that tolcapone dosages of 100 mg three times daily and 200 mg three times daily are well tolerated and equally effective in improving function in L-Dopa-treated nonfluctuating patients with PD.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be useful in the treatment of depression in patients with Parkinson's disease (PD). However, a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs. So far, no prospective trial comparing the effects of different SSRIs in depressed patients with PD has been performed. The aim of the present study was to assess the effects of four SSRIs (citalopram, fluoxetine, fluvoxamine, and sertraline) on motor performance and their efficacy on depression in a group of patients with PD. Sixty-two consecutive nondemented, nonfluctuating, depressed patients with PD were included in four treatment groups (15 patiens received citalopram, 16 fluoxetine, 16 fluvoxamine, and 15 sertraline). The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory, and Hamilton Depression Rating Scale at baseline and after 1, 3, and 6 months. Fifty-two patients completed the study. UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied. A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs (Beck and Hamilton scores improving;p< 0.05 according to an analysis of variance). Our findings suggest that SSRIs do not significantly worsen extrapyramidal symptomatology and may ameliorate depression in patients with PD.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The present study describes two patients, both of Yemenite origin, with catatonic schizophrenia who responded to treatment with risperidone. One had a long history of psychiatric disorder, whereas the other was a first-episode, drug-naive patient. Our observation agrees with previous reports on the use of risperidone and other novel neuroleptic agents in the treatment of catatonia of different etiologies.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A 71-year-old woman presented with severe akinesia, frozen gait, and compromised postural reflexes, without rigidity, tremor, or vertical gaze disturbance. With a working diagnosis of pure akinesia, we administered amantadine (150 mg/d) and L-threo-3,4-dihydroxyphenylserine (DOPS) (600 mg/d), which alleviated her symptoms. When frozen gait recurred 2 months later, we increased the dose of L-threo-DOPS to 900 mg/d and added levodopa (300 mg/d) combined with carbidopa, but this failed to improve the patient's symptoms. We then combined administration of tandospirone, a serotonin (5-HT) 1A agonist with L-threo-DOPS (600 mg/d), resulting in marked clinical improvement. Tandospirone is reported to activate noradrenergic neurons via the 5-HT 1A receptor, which could account for such striking improvement in a patient previously responsive to the noradrenergic precursor L-threo-DOPS given alone.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

This study investigated whether chronic coadministration of &agr;-dihydroergocryptine (DHEC) altered the plasma pharmacokinetics of individualized treatments with levodopa in 12 patients with Parkinson's disease. Steady-state pharmacokinetics of plasma levodopa (L-Dopa) under combined treatment were compared with those under treatment with L-Dopa alone. There was no evidence of increased exposure to L-Dopa caused by concomitant treatment with DHEC. In contrast, additional treatment with DHEC reduced the overall exposure to L-Dopa (17.5% reduction in area under the curve; 95% CI: 23%–6%). This effect was small but statistically significant for the area under the plasma concentration–time curve, whereas tmax(time of maximum plasma concentration) and peak-to-trough fluctuation were not affected. Cmax(maximum plasma concentration), on average, was reduced to a similar extent (−14.5%; 95% CI: 38% to −17%), albeit not significantly. The magnitude of the interaction does not suggest changing the current clinical practice of up-titrating DHEC and subsequently adapting L-Dopa to the individual needs of patients.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Phenytoin toxicity continues to be a common medical problem. It can present with subtle and atypical symptoms. Herein the authors report what is, to their knowledge, the first case in the literature of phenytoin toxicity that manifested solely in the form of hypothermia.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Amoxapine, a dibenzoxazepine antidepressant, has been suggested to have atypical antipsychotic properties. We tested it to control psychosis in three patients with Parkinson's disease (PD). Two patients had significant improvement in hallucinations, whereas the third could not tolerate the drug for a sufficient period. All three patients experienced a decline in motor function; two also had concomitant reduction in dyskinesias. Therefore, although we found some support for amoxapine having antipsychotic properties, this drug seems to carry a risk of worsening motor function in patients with PD.

ISSN:0362-5664    

出版商:OVID    

年代:2001

数据来源: OVID